It is concluded that α2-adrenoceptors may be promising targets in the antipsychotic therapy.

Simple SummaryFood deprivation protocols are frequently used in behavioral studies. However, there is limited evidence as to when food deprivation compromises animal welfare. Regarding the refinement of experiments involving animals, this study investigated the effects of food deprivation on body weight loss and behavior in male and female rats. Sex difference in behavior and motivational state after food deprivation is the main finding of the study. The data highlights the need for tailored pilot experiments to evaluate the impact of food deprivation on animals with regard to the 3Rs principles (replacement, reduction, refinement) in animal science.AbstractIn behavioral studies, food deprivation protocols are routinely used to initiate or maintain motivational states that are required in a particular test situation. However, there is limited evidence as to when food deprivation compromises animal welfare. This study investigated the effects of different lengths of food deprivation periods and restricted (fixed-time) feeding on body weight loss as well as anxiety-related and motivated behavior in 5–6 month old male and female Wistar rats. The observed body weight loss was not influenced by sex and ranged between 4% (16 h deprivation) to approximately 9% (fixed-time feeding). Despite significant body weight loss in all groups, the motivation to eat under the aversive test conditions of the modified open field test increased only after 48 h of food deprivation. Long-lasting effects on anxiety as measured in the elevated plus maze test 24 h after refeeding have not been observed, although fixed-time feeding could possibly lead to a lasting anxiogenic effect in female rats. Overall, female rats showed a more anxiolytic profile in both tests when compared to male rats. Despite these sex differences, results suggest that food deprivation is not always paralleled by an increased motivation to feed in a conflict situation. This is an important finding as it highlights the need for tailored pilot experiments to evaluate the impact of food deprivation protocols on animals in regard to the principles of the 3Rs introduced by Russell and Burch.

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Dopaminergic, serotonergic, and adrenergic receptors are targets for therapeutic actions in schizophrenia. Dopamine D 2 receptor partial agonists such as aripiprazole represent a treatment option for patients with this severe disorder. The ineffectiveness of terguride, another D 2 receptor partial agonist, in treating schizophrenia was recently attributed to its considerably high intrinsic activity at D 2 receptors. In this study, we used functional assays for recombinant D 2 receptors and native 5-hydroxytryptamine 2A (5-HT 2A ), a 2C -adrenergic, and histamine H 1 receptors to compare the pharmacological properties of terguride and three of its halogenated derivatives (2-chloro-, 2-bromo-, 2-iodoterguride) with those of aripiprazole. Subsequently, we studied the antidopaminergic effects of 2-bromoterguride using amphetamine-induced locomotion (AIL (hD 2S ) receptors that were half as high as the intrinsic activity for terguride; aripiprazole lacked agonist activity. 2-Bromoterguride and aripiprazole activated D 2S receptor-mediated inhibition of cAMP accumulation to the same extent; intrinsic activity was half as high as that of terguride. All compounds tested behaved as antagonists at human D 2long /Ga o (hD 2L /Ga o ) receptors. Compared with aripiprazole, terguride and its derivatives displayed higher affinity at porcine 5-HT 2A receptors and a 2C -adrenoceptors and lower affinity at H 1 receptors. 2-Bromoterguride inhibited AIL and did not induce catalepsy in rats. Because of its in vitro and in vivo properties, 2-bromoterguride may be a strong candidate for the treatment of schizophrenia with a lower risk to induce EPS.

Mice deficient in the alpha subunit of G(z) show enhanced sensitivity to the disruption of PPI and locomotor hyperactivity caused by dopaminergic stimulation. These results suggest a possible role for G(z) in neuropsychiatric illnesses with presumed dopaminergic hyperactivity, such as schizophrenia.

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